The objectives of this proposal are (1) to delineate the barriers to the passage of macromolecules during ultrafiltration in the normal glomerulus and (2) to determine the mechanisms responsible for disturbances of glomerular barrier function in proteinuric states, and (3) to isolate component cells of the glomerulus and to try and establish some functional aspects of these cells in in vitro systems. An important aspect is the ultrastructural identification of endogenous protein distribution (using peroxidase-labelled FAB fragments of antibodies against rat albumin or IgG) under physiological hemodynamic flow conditions (using Munich-Wistar rats with superficial glomeruli, on or close to the renal surface, and thus accessible to rapid fixation in situ). By a correlation of the morphologic findings with parallel functional data for normal and nephrotic glomeruli the proposed studies aim to clarify the dynamics of normal and abnormal glomerular permeability in relation to structure. Furthermore, by isolating and characterizing component cells of the glomerulus, it is hoped to obtain functional information regarding these cells and their role in glomerular function. A phagocytic cell has been isolated from the glomerulus and the question at present being investigated is whether this cell is the sole mesangial cell or whether there are other types present; the epithelial cell has been positively characterized and established in culture.